DESCRIPTION

FLUORESCITE® (fluorescein injection, USP) 10% contains fluorescein sodium (equivalent to
fluorescein 10% w/v). It is a sterile solution for use intravenously as a diagnostic aid. Its chemical name
is spiro[isobenzofuran-1(3H ),9'-[9H]xanthene]-3-one, 3'6'-dihydroxy, disodium salt. The active
ingredient is represented by the chemical structure:

FLUORESCITE® (fluorescein injection, USP) 10% is supplied as a sterile, unpreserved, unit dose
aqueous solution, that has a pH of 8.0 – 9.8 and an osmolality of 572-858 mOsm/kg.

DOSAGE AND ADMINISTRATION

Dosing

For children, the dose should be calculated on the basis of 7.7 mg for each kg of actual body weight (or
35 mg for each 10 pounds of body weight) up to a maximum of 500 mg via intravenous administration.

Preparation For Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration. Do not mix or dilute with other solutions or drugs. Flush intravenous cannulas before
and after drugs are injected to avoid physical incompatibility reactions.

Administration

Inject the dose rapidly (1 mL per second is normally recommended) intravenously into the antecubital
vein, after taking precautions to avoid extravasation. A syringe, filled with FLUORESCITE® , may be
attached to transparent tubing and a 23 gauge butterfly needle for injection. Insert the needle and draw
the patient’s blood to the hub of the syringe so that a small air bubble separates the patient’s blood in the
tubing from the fluorescein. With the room lights on, slowly inject the blood back into the vein while
watching the skin over the needle tip. If the needle has extravasated, the patient’s blood will be seen to
bulge the skin and the injection should be stopped before any fluorescein is injected. When assured that
extravasation has not occurred, the room light may be turned off and the fluorescein injection
completed. Luminescence usually appears in the retina and choroidal vessels in 7 to 14 seconds and can
be observed by standard viewing equipment.

Reduction in dose from 5 mL to 2 mL of FLUORESCITE® Injection 10% may be appropriate in cases
when a highly sensitive imaging system e.g., scanning laser ophthalmoscope is used.

HOW SUPPLIED

Dosage Forms And Strengths

Single use 5 mL vial containing 100 mg/mL fluorescein.

Storage And Handling

FLUORESCITE® (fluorescein injection, USP) 10% is supplied in a single use 5 mL glass vial with a
gray FluroTec coated chlorobutyl stopper and purple flip-off aluminum seal. The vial stopper is not
made with natural rubber latex. The vial contains a sterile, red-orange solution of fluorescein sodium.

SIDE EFFECTS

Skin And Urine Discoloration

The most common reaction is temporary yellowish discoloration of the skin and urine. Urine may attain
a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine
in 24 to 36 hours.

Gastrointestinal Reactions

Nausea, vomiting, and gastrointestinal distress are common adverse events. A strong taste may develop
after injection.

Hypersensitivity Reactions

Symptoms and signs of hypersensitivity have occurred. Generalized hives and itching, bronchospasm
and anaphylaxis have been reported. Rare cases of death have been reported. [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

WARNINGS

PRECAUTIONS

Resiratory Reactions

Caution is to be exercised in patients with a history of allergy or bronchial asthma. An emergency tray
should be available in the event of possible reaction to FLUORESCITE® Injection 10%.

If a potential allergy is suspected, an intradermal skin test may be performed prior to intravenous
administration, i.e., 0.05 mL injected intradermally to be evaluated 30 to 60 minutes following injection.
Given the sensitivity and specificity of skin testing, a negative skin test is not proof that a patient is not
allergic to fluorescein.

Severe Local Tissue Damage

Care must be taken to avoid extravasation during injection as the high pH of fluorescein solution can
result in severe local tissue damage. The following complications resulting from extravasation of
fluorescein have been noted to occur: severe pain in the arm for several hours, sloughing of the skin,
superficial phlebitis, subcutaneous granuloma, and toxic neuritis along the median curve in the
antecubital area. When significant extravasation occurs, the injection should be discontinued and
conservative measures to treat damaged tissue and to relieve pain should be implemented. [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].

Nausea And/Or Vomiting

Nausea and/or vomiting and gastrointestinal distress occur commonly within the first few minutes
following injection. These reactions usually subside within 10 minutes.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

There have been no long-term studies done using fluorescein in animals to evaluate carcinogenic
potential.

Use In Specific Populations

Pregnancy

Adequate animal reproduction studies have not been conducted with fluorescein sodium. It is also not
known whether fluorescein sodium can cause fetal harm when administered to a pregnant woman.
Fluorescein sodium should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Fluorescein sodium injection has been demonstrated to be excreted in human milk for up to 4 days.
Following fluorescein angiography, breast-feeding should therefore be discontinued for at least 4 days
and the milk should be pumped off and discarded during this period.

Pediatric Use

Pediatric patients have been included in clinical studies. No overall differences in safety or
effectiveness have been observed between pediatric and adult patients.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and other adult
patients.

OVERDOSE

No Information Provided

CONTRAINDICATIONS

FLUORESCITE® Injection 10% is contraindicated in patients with known hypersensitivity to
fluorescein sodium or any other ingredients in this product. Rare cases of death due to anaphylaxis have
been reported. [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Fluorescein sodium can induce serious intolerance reactions. These reactions of intolerance are always
unpredictable but they are more frequent in patients who have previously experienced an adverse
reaction after fluorescein injection (symptoms other than nausea and vomiting) or in patients with history
of allergy such as food or drug induced urticaria, asthma, eczema, allergic rhinitis.

Detailed questioning of each patient is recommended before the angiography to evaluate any prior
history of allergy.

CLINICAL PHARMACOLOGY

Mechanism Of Action

Fluorescein sodium responds to electromagnetic radiation and light between the wavelengths of 465-
490 nm and fluoresces, i.e., emits light at wavelengths of 520-530 nm. Thus, the hydrocarbon is excited
by blue light and emits light that appears yellowish-green. Following intravenous injection of
fluorescein sodium in an aqueous solution, the unbound fraction of the fluorescein can be excited with a
blue light flash from a fundus camera as it circulates through the ocular vasculature, and the yellowish
green fluorescence of the dye is captured by the camera. In the fundus, the fluorescence of the dye
demarcates the retinal and/or choroidal vasculature under observation, distinguishing it from adjacent
areas/structures.

Pharmacokinetics

Distribution

Within 7 to 14 seconds after intravenous (IV) administration into antecubital vein, fluorescein usually
appears in the central artery of the eye. Within a few minutes of IV administration of fluorescein
sodium, a yellowish discoloration of the skin occurs, which begins to fade after 6 to 12 hours of
dosing. Various estimates of volume of distribution indicate that fluorescein distributes well into
interstitial space (0.5 L/kg).

Metabolism

Fluorescein undergoes rapid metabolism to fluorescein monoglucuronide. After IV administration of
fluorescein sodium (14 mg/kg) to 7 healthy subjects, approximately 80% of fluorescein in plasma was
converted to glucuronide conjugate after a period of 1 hour post dose, indicating relatively rapid
conjugation.

Excretion

Fluorescein and its metabolites are mainly eliminated via renal excretion. After IV administration, the
urine remains slightly fluorescent for 24 to 36 hours. A renal clearance of 1.75 mL/min/kg and a hepatic
clearance (due to conjugation) of 1.50 mL/min/kg have been estimated. The systemic clearance of
fluorescein was essentially complete by 48 to 72 hours after administration of 500 mg fluorescein.

PATIENT INFORMATION

After administration of fluorescein sodium, skin will attain a temporary yellowish discoloration. Urine
attains a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades
in urine in 24 to 36 hours. [see ADVERSE REACTIONS]

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.